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Wednesday, October 24, 2018

Acetazolamide in Cryptococcal Meningitis


Rationales to use / Dosing Recommended



After 4 days, if the pressure remained elevated, acetazolamide could be added at a dose of 250 mg/6 h orally. Corticosteroids were allowed at doses of up to 50 mg/day of hydrocortisone to alleviate reactions to the amphotericin B infusions.

Treatment of elevated CSF pressure in granulomatous meningitis is aimed at decompressing the fluid, either by ventricular drainage or by medical means, such as treatment with acetazolamide or mannitol. These agents reduce secretion of the CSF or render the plasma relatively hypertonic, thus causing an osmotic gradient from the CSF to the plasma.



(Renal Adjustment)

For patients who weighed >45 kg, the starting dosage was 1 tablet given every 6 h. The dose interval was reduced according to serum creatinine level, as follows: the interval was reduced to 12 h for patients with a serum creatinine level of 186–266 μM and to 24 h for those with a serum creatinine level of 267–354 μM; no tablets were given to patients whose level increased to >354 μM.


(Weight)

 For patients who weighed 35–45 kg, the starting dosage was 1 tablet given every 8 h; the dose interval was reduced to 24 h for patients with a serum creatinine level of 186–266 μM, and no tablets were given to patients whose level increased to >266 μM. Oral potassium supplements were given if the patient's serum potassium level decreased to <3.0 mM, and bicarbonate supplements were provided if the venous bicarbonate level decreased to <15 mM.



For the patient with cryptococcal meningitis, a 2-month course of acetazolamide therapy at a total dose of 500 mg/day was associated with resolution of the papilledema and restoration of visual acuity. The patient with C. immitis meningitis required 4 years of acetazolamide therapy; intermittent discontinuation of acetazolamide resulted in recurrence of headaches and visual disturbances. No significant electrolyte abnormalities or adverse events were observed. The papilledema did not recur after the cessation of therapy.

Chronically elevated ICP may lead to serious sequelae, including visual and hearing loss, systemic hypertension, severe cephalgia, and depressed mentation.

* Acetazolamide may be used to reverse chronically elevated ICP due to fungal meningitides and deserves further investigation.



Franks Shann - 5-10 mg/kg (Adult 100-250mg) q6-8H




Rationales NOT to use



Discussion. This evaluation of acetazolamide for the treatment of elevated intracranial pressure complicating cryptococcal meningitis was terminated prematurely, because independent review strongly suggested that acetazolamide therapy was harmful, with an excess of severe acidosis and adverse events. This study has insufficient power to characterize the effect, if any, of acetazolamide on intracranial pressure, headache, or Karnofsky score. The severity of the acidosis, combined with hypokalemia, suggests that acetazolamide has an additive or synergistic toxicity with amphotericin B resulting from renal tubular dysfunction.

The antisecretory effects of acetazolamide may be insufficient to reduce intracranial pressure in the face of severe outflow obstruction (caused by cryptococci or capsular polysaccharide) of CSF drainage through the arachnoid villi [2]. Acetazolamide should not be used in combination with amphotericin B for the treatment of cryptococcal meningitis. This study does not address whether acetazolamide may be beneficial for patients receiving lipid formulations of amphotericin B; for HIV-negative patients; for the palliation of symptoms of elevated intracranial pressure, if used in areas where amphotericin B is not affordable [10]; or after the amphotericin B course has finished.



https://emedicine.medscape.com/article/215354-overview / UptoDate: Cryptococcus neoformans: Treatment of meningoencephalitis and disseminated infection in HIV seronegative patients

Mannitol has no proven value in reducing pressure in cryptococcal meningitis. Acetazolamide or corticosteroids to control CSF pressure unassociated with immune reconstitution inflammatory syndrome (IRIS) should also be avoided.



A Randomized, Double‐Blind, Placebo‐Controlled Trial of Acetazolamide for the Treatment of Elevated Intracranial Pressure in Cryptococcal Meningitis   

[ Newton et al.   -   35(6):769-72 · September 2002 ] 

We conducted a trial of oral acetazolamide for the treatment of cryptococcal meningitis in 22 Thai adults with headache and an opening cerebrospinal fluid pressure of >/=200 mm H(2)0. The trial was terminated prematurely because patients who received acetazolamide developed significantly lower venous bicarbonate levels and higher chloride levels and had more-frequent serious adverse events than did subjects who received placebo.




Acetazolamide should not be used as therapy for increased ICP management since it may cause hyperchloremic acidosis and does not result in a decrease in ICP (AI)

- All accessed on 24/10/2018 -

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